Background: Mitochondrial calcium uniporter regulator 1 (MCUR1, also known as CCDC90A) is a protein-coding gene that plays a key role in mitochondrial calcium uptake. However, knowledge about its clinical significance in breast cancer is still limited. Methods: The expression profile of MCUR1 in various cancers was analyzed via the ONCOMINE and Tumor Immune Estimation Resource databases. The correlation between MCUR1 expression and the clinical features of breast cancer was investigated using UALCAN and MEXPRESS. Immunohistochemical analysis was applied to verify the expression of MCUR1 in breast cancer. The prognostic significance of MCUR1 in breast cancer was evaluated using Kaplan-Meier plotter and the PrognoScan database. Gene Set Enrichment Analysis (GSEA) was performed to explore the possible biological functions of MCUR1. In addition, the function of MCUR1 was examined by gene silencing in vitro. Western blotting was applied to detect the expression of proteins. Results: MCUR1 was overexpressed in breast cancer and significantly related to the clinical characteristics of breast cancer. Results from the public databases and IHC analysis indicated that MCUR1 expression was the highest in triple-negative breast cancer (TNBC). The high expression of MCUR1 was associated with poor overall survival, distant metastasis-free survival, and recurrence-free survival. GSEA showed that the hypoxia pathway, cellular reactive oxygen species (ROS) pathway, epithelial-mesenchymal transition pathway, and notch signaling pathway were differentially enriched in the high MCUR1 expression phenotype. In vitro experiments showed that MCUR1 knockdown in TNBC cell lines led to a decrease in cellular ROS and weakened cell migration and invasion abilities. Moreover, Western blotting showed that MCUR1 knockdown inhibited the epithelial-mesenchymal transition of TNBC cells via the ROS/Nrf2/Notch pathways. Conclusion: Our study suggests that MCUR1 plays a pivotal role in the malignant progression of breast cancer.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82072895]
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Obstet & Gynecol, Canc Biol Res Ctr,Key Lab,Tongji Hosp,Minist Educ, Wuhan, Hubei, Peoples R China
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Obstet & Gynecol, Canc Biol Res Ctr,Key Lab,Tongji Hosp,Minist Educ, Wuhan, Hubei, Peoples R China[2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Obstet & Gynecol, Wuhan, Hubei, Peoples R China
推荐引用方式(GB/T 7714):
gao peipei,peng ting,lin shitong,et al.Key Role of MCUR1 in Malignant Progression of Breast Cancer[J].ONCOTARGETS AND THERAPY.2021,14:4163-4175.doi:10.2147/OTT.S306854.
APA:
gao,peipei,peng,ting,lin,shitong,zhi,wenhua,cao,canhui...&ding,wencheng.(2021).Key Role of MCUR1 in Malignant Progression of Breast Cancer.ONCOTARGETS AND THERAPY,14,
MLA:
gao,peipei,et al."Key Role of MCUR1 in Malignant Progression of Breast Cancer".ONCOTARGETS AND THERAPY 14.(2021):4163-4175